The human skin consists of two major layers, the bottom thicker layer (dermis) and the top thinner layer (epidermis). Dermis is the layer which provides the strength, elasticity and the thickness to the skin.
The main cell type of the dermis is the fibroblast, which is responsible for synthesis and secretion of all the dermal matrix components such as collagen, elastin and glycosaminoglycans. Collagen provides the strength, elastin the elasticity and glycosaminoglycans the moistness and plumpness of the skin. With ageing, the thickness of the dermal layer is reduced and this is believed to be partially responsible for the formation of wrinkles in ageing skin. The top layer of human skin or the epidermis which provides the resilience and the barrier properties of the skin, is composed of many different cell types including keratinocytes, melanocytes and langerhans cells. Keratinocyte is the major cell type of the epidermis (75-80% of the total number of cells in the human epidermis). Richards et al. reported that estrogen stimulates secretion of a protein, prolactin, by human dermal fibroblast cells and that prolactin then stimulates proliferation of keratinocytes (Richards et al., Human Dermal Fibroblasts Express Prolactin In Vitro., J. Invest. Dermatol. (1996), 106: 1250).
Estrogens and synthetic compounds which act like estrogens are known to increase the thickness of the dermal layer and to reduce wrinkle formation in the ageing skin. The changes in the skin such as skin dryness, loss of skin elasticity and plumpness occurring after menopause is attributed to the lack of estrogen production. Estrogen therapy prevents or slows down many of these changes associated with ageing skin (Creidi et al., “Effect of a conjugated estrogen cream on ageing facial skin”, Maturitas, (1994) 19, p. 211). Some of the effects of estrogen on skin include: increase in skin thickness and disappearance of fine wrinkles, increase of the mitotic rate of the epidermis, reduction in the size and activity of the sebaceous gland, slow down of the rate of hair growth, stimulation of collagen turnover and increase in the production of hyaluronic acid and glycosaminoglycan synthesis of the fibroblasts (Pugliese, Menopausal skin, Skin Inc., March/April 1994: p 69-77).
Schmidt et al. report on the effects on ageing skin of the face of perimenopausal females treated with a 0.3% estriol cream or with a 0.01% estradiol cream for 6 months (Schmidt et al., “Treatment of skin ageing symptoms in perimenopausal females with estrogen compounds. A pilot study”, Maturitas (1994), 29(1), 25-30). Both treatment groups were found to show improvement of the various skin ageing symptoms at the end of treatment. The effects of the group treated with topical estriol were deemed to be slightly superior with regard to their extent and onset.
Shah et al. (“Estrogen and skin. An overview”, Am J Clin Dermatol (2001); 2(3):143-150) report that topical and systemic estrogen therapy can increase the skin collagen content and therefore maintain skin thickness. In addition, it is said that estrogen maintains skin moisture by increasing acid mucopolysaccharides and hyaluronic acid in the skin and possibly maintaining stratum corneum barrier function. Furthermore it is observed that estrogen may increase cutaneous wound healing by regulating cytokine levels as topical estrogen has been found to accelerate and improve wound healing in elderly men and women.
In a review article by Sitruk-Ware et al. (“Topical hormonal treatment and urogenital atrophy”, Schweiz Rundsch Med Prax (1997) August 13; 86(33):1245-1248) it is stated that local estrogen therapies are recommended for the treatment of complaints due to vulvar and vaginal atrophy. Estrogens specifically mentioned in the review article include estrone, promestriene, estradiol and estriol.